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Combined Effects of GLP-1 Analogue and Exercise on Maintenance of Weight Loss and Health After Very-low Calorie Diet (S-LITE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04122716
Recruitment Status : Active, not recruiting
First Posted : October 10, 2019
Last Update Posted : April 21, 2020
Sponsor:
Collaborators:
Hvidovre University Hospital
University of Oxford
Karolinska Institutet
Information provided by (Responsible Party):
Signe Torekov, University of Copenhagen

Brief Summary:

Introduction: The success rate of weight loss maintenance is limited. Therefore, the purpose of this study is to investigate the maintenance of weight loss and immunometabolic health outcomes after diet-induced weight loss followed by one-year treatment with a glucagon-like peptide-1 receptor agonist (liraglutide), physical exercise, or the combination of both treatments as compared with placebo in individuals with obesity.

Methods and analysis: This is an investigator-initiated, randomized, placebo-controlled, parallel group trial. The investigators will enroll women and men (age 18 to 65 years) with obesity (body mass index 32 to 43 kg/m2) to adhere to a very low-calorie diet (800 kcal/day) for eight weeks in order to lose at least 5 % of body weight. Subsequently, participants will be randomized in a 1:1:1:1 ratio to one of four study groups for 52 weeks: 1) placebo, 2) exercise 150 min/week + placebo, 3) liraglutide 3.0 mg/day, and 4) exercise 150 min/week + liraglutide 3.0 mg/day. Re-screening is allowed within the recruitment period.

The primary endpoint is change in body weight from randomization to end-of-treatment.

Ethics and dissemination: The trial has been approved by the ethical committee of the Capital Region of Denmark (H-16027082) and the Danish Medicines Agency (EudraCT 2015-005585-32). The trial will be conducted in agreement with the Declaration of Helsinki and monitored to follow the guidelines for good clinical practice. Results will be submitted for publication in international peer-reviewed scientific journals.


Condition or disease Intervention/treatment Phase
Obesity Drug: Liraglutide Behavioral: Exercise Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 215 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: After 8 weeks of weight loss the participants are randomized to receive a) Liraglutide 3mg/day sc or b) placebo sc or c) Exercise + placebo sc or d) Exercise + Liraglutide 3mg/d sc for 52 weeks.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The above-mentioned are masked in terms of Liraglutide/placebo, not in terms of exercise/non-exercise.

Statistical analysis of primary outcome will be blinded to the assessor.

Primary Purpose: Treatment
Official Title: Synergy Effect of the Appetite Hormone GLP-1 (LiragluTide) and Exercise on Maintenance of Weight Loss and Health After a Low Calorie Diet - the S-LiTE Randomized Trial
Actual Study Start Date : September 2016
Actual Primary Completion Date : November 2019
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Active Comparator: Liraglutide + exercise

Liraglutide: 3 mg/day sc. The GLP-1 RA, liraglutide (3.0 mg), or placebo, will be administrated once daily as subcutaneous injections in the abdomen or thigh. The starting dose is 0.6 mg with weekly increments of 0.6 mg until 3.0 mg is achieved. The titration procedure will be prolonged for participants who do not tolerate fast up-titration. Participants who do not tolerate the 3.0 mg dose may in special circumstances stay at lower dose (2.4 mg). However, the aim is to reach 3.0 mg for all study participants.

Exercise: 150 min of moderate intensity, 75 min of vigorous intensity, or an equivalent combination of moderate and vigorous intensity exercise per week in accordance with WHO recommendations.

Drug: Liraglutide

Daily injections (3mg) with weight consultations starting at dose of 0.6 mg injections with 0.6 mg increments weekly until 3.0 mg is achieved. For subjects who do not tolerate the fast weekly up-titration of 0.6 mg study drug until the 3mg, the titration procedure can be prolonged with up to three weeks for each up-titration.

Subjects who do not tolerate the 3mg dose may in special circumstances stay at 2.4 mg, however the overall aim is to reach 3 mg for all study subjects.

The dosage and up-titration follow the recommendations from the summary of product characteristics.

Other Name: Saxenda

Behavioral: Exercise

150 min of moderate intensity, 75 min of vigorous intensity, or an equivalent combination of moderate and vigorous intensity exercise per week in accordance with WHO recommendations.

Exercise prescription will be performed under strict control of the scientific personnel.

There will be aerobic exercise and will include 4 sessions per week after the ramp-in period.

2 sessions per week will be performed under supervision of the staff and 2 sessions will be performed individually but monitored by the staff.

Supervised sessions include structured exercise with a duration of 45 min. Of this 30 min will comprise of interval-based spinning session and 15 min circuit training program focusing on large muscle groups.

Individual exercise includes aerobic exercise and general physical activity (e.g brisk walking and cycling to work).

Participants will use heart rate monitors during sessions.


Liraglutide + non-exercise

Liraglutide: 3 mg/day sc. The GLP-1 RA, liraglutide (3.0 mg), or placebo, will be administrated once daily as subcutaneous injections in the abdomen or thigh. The starting dose is 0.6 mg with weekly increments of 0.6 mg until 3.0 mg is achieved. The titration procedure will be prolonged for participants who do not tolerate fast up-titration. Participants who do not tolerate the 3.0 mg dose may in special circumstances stay at lower dose (2.4 mg). However, the aim is to reach 3.0 mg for all study participants.

Non-exercise: Participants should stay at same physical activity level (i.e. max. 2 h of vigorous endurance training/week) as when the participant was included in the study.

Drug: Liraglutide

Daily injections (3mg) with weight consultations starting at dose of 0.6 mg injections with 0.6 mg increments weekly until 3.0 mg is achieved. For subjects who do not tolerate the fast weekly up-titration of 0.6 mg study drug until the 3mg, the titration procedure can be prolonged with up to three weeks for each up-titration.

Subjects who do not tolerate the 3mg dose may in special circumstances stay at 2.4 mg, however the overall aim is to reach 3 mg for all study subjects.

The dosage and up-titration follow the recommendations from the summary of product characteristics.

Other Name: Saxenda

Placebo + exercise

Placebo: 3mg/day sc.

Exercise: 150 min of moderate intensity, 75 min of vigorous intensity, or an equivalent combination of moderate and vigorous intensity exercise per week in accordance with WHO recommendations.

Behavioral: Exercise

150 min of moderate intensity, 75 min of vigorous intensity, or an equivalent combination of moderate and vigorous intensity exercise per week in accordance with WHO recommendations.

Exercise prescription will be performed under strict control of the scientific personnel.

There will be aerobic exercise and will include 4 sessions per week after the ramp-in period.

2 sessions per week will be performed under supervision of the staff and 2 sessions will be performed individually but monitored by the staff.

Supervised sessions include structured exercise with a duration of 45 min. Of this 30 min will comprise of interval-based spinning session and 15 min circuit training program focusing on large muscle groups.

Individual exercise includes aerobic exercise and general physical activity (e.g brisk walking and cycling to work).

Participants will use heart rate monitors during sessions.


No Intervention: Placebo + non-exercise

Placebo: 3mg/day sc.

Non-exercise: Participants should stay at same physical activity level (i.e. max. 2 h of vigorous endurance training/week) as when the participant was included in the study.




Primary Outcome Measures :
  1. Body weight change (kg) [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Weight will be measured to the nearest 0.1 kg. The same set of scales should ideally be used throughout the trial. Weight should be measured in a fasting state without shoes and wearing light clothes.


Secondary Outcome Measures :
  1. Body composition (fat mass and fat free mass) [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Dual-energy X-ray absorptiometry (DXA) scans will be performed in fasting state to measure body fat mass and fat free mass.

  2. Waist and hip circumference [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Waist circumference, the midpoint between lowest rib and iliac crest, and hip circumference, the level of the great trochanters, will be measured in duplicate to the nearest 0.1 cm after gentle expiration.

  3. Hormonal regulation of blood glucose [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Measured from blood samples

  4. Lipids [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Measured from blood samples (e.g. cholesterol (HDL, LDL, VLDL) and triglycerides (TG)) (mmol/L)

  5. Blood pressure [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Blood pressure will be measured in duplicate from the non-dominant arm with a digital blood pressure monitor in sitting position after at least 5 min of rest (mmHg).

  6. Metabolic Syndrome [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Relevant clinical parameters (lipids, fasting glucose, waist circumference, and blood pressure) will be used to investigate whether the participants have metabolic syndrome (yes or no).

  7. MetS z-score [ Time Frame: Change from baseline to end-of-treatment (52 weeks) ]
    Relevant clinical parameters (lipids, fasting glucose, waist circumference, and blood pressure) will be used to calculate a MetS z-score for men and women, respectively



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • BMI > 32 and < 43 (kg/m2)
  • Age >18 and <65 years
  • Safe contraceptive method

Exclusion Criteria:

  • Patients diagnosed with known serious chronic illness including type 1 or 2 diabetes (or a randomly measured fasting plasma glucose > 7 mmol/l)
  • Angina pectoris, coronary heart disease, congestive heart failure (NYHA III-IV)
  • Severe renal impairment (creatinine clearance (GFR) <30 mL/min)
  • Severe hepatic impairment
  • Inflammatory bowel disease
  • Gastroparesis
  • Cancer
  • Chronic obstructive lung disease
  • Psychiatric disease, a history of major depressive or other severe psychiatric disorders
  • The use of medications that cause clinically significant weight gain or loss
  • Previous bariatric surgery
  • A history of idiopathic acute pancreatitis
  • A family or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma
  • Osteoarthritis which is judged to be too severe to manage the exercise programme. As intended per study design the intervention will include a 5% weight loss prior to randomization, thus it is expected that possible participants with mild form of osteoarthritis will be able to manage exercise prescriptions.
  • Pregnancy, expecting pregnancy or breast feeding. If a study participant is in doubt whether she could be pregnant, a urine pregnancy test is performed. Females of childbearing potential who are not using adequate contraceptive methods (as required by local law or practice). Adequate contraception must be used throughout the study period and at least 65 hours after discontinuation of trial medication (65 hours corresponds to 5 times the half-life of Saxenda). Allergy to any of the ingredients/excipients.
  • Allergy to any of the ingredients/excipients of the study medication: liraglutide, disodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid, sodium hydroxide.
  • Regular exercise training at high intensity (e.g. spinning) >2 hours per week.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04122716


Locations
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Denmark
University of Copenhagen, Department of Biomedical Sciences
Copenhagen, Denmark, 2200
Sponsors and Collaborators
Signe Torekov
Hvidovre University Hospital
University of Oxford
Karolinska Institutet
Investigators
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Study Director: Signe S Torekov, Prof, PhD University of Copenhagen
Principal Investigator: Sten Madsbad, Prof, MD Hvidovre University Hospital
  Study Documents (Full-Text)

Documents provided by Signe Torekov, University of Copenhagen:
Statistical Analysis Plan  [PDF] March 4, 2020

Publications:
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE, Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM, Yanovski SZ, Jordan HS, Kendall KA, Lux LJ, Mentor-Marcel R, Morgan LC, Trisolini MG, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014 Jun 24;129(25 Suppl 2):S102-38. doi: 10.1161/01.cir.0000437739.71477.ee. Epub 2013 Nov 12. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S139-40.

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Responsible Party: Signe Torekov, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT04122716    
Other Study ID Numbers: U 1111-1173-3104 (UTN)
2015-005585-32 ( EudraCT Number )
H-16027082 ( Other Identifier: The Ethical Committee of the Capital Region of Denmark )
First Posted: October 10, 2019    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020

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Product Manufactured in and Exported from the U.S.: No
Keywords provided by Signe Torekov, University of Copenhagen:
Weight loss maintenance
Immunometabolic health
Exercise intervention
GLP-1 receptor agonist (liraglutide)
Additional relevant MeSH terms:
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Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists